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The impending threat of antibiotic resistance

Antibiotic Research UK is the BIA's charity of 2015, but what does it intend to do?

Microbiological culture

The spread of bacteria resistant to antibiotics is an important health threat, far greater than the threat posed by the current Ebola outbreak as potentially every UK citizen could be affected. Antibiotic resistance means that antibiotics may no longer work when prescribed to treat infections. Unlike other drugs used in medicine, the more we use antibiotics the less effective they become.

Antibiotic resistance is not a new problem, but has been around since the discovery and first use of penicillin in the 1940's. In the past, resistance was not regarded as a major health problem as new antibiotics were regularly developed and could be used to treat infections caused by bacteria resistant to drugs already widely in use. What is different today is that there are hardly any new antibiotics being developed, so we are unable to rely on new treatments becoming available to treat these resistant bacteria.

In the pre-antibiotic era, death from infection was very common as shown in the table below.

Causes of death by infection in the pre-antibiotic era 

9 women in 1000 die in childbirth - 40% from sepsis
Infant mortality
Up to 30% of children died before their first birthday
Serious skin infection
1 in 9 people died from something as simple as a cut or scrape
1 in 3 people died
Ear infection
Caused deafness
High death rate. Up to one 1 in 3 people killed in WW1 died from infection
Life expectancy
At least 20 years less than currently before antibiotics were introduced

Report To The President On Combating Antibiotic Resistance, 2014

Many patients are at increased risk of getting antibiotic resistant infections as a consequence of the treatment they receive for other medical conditions. Medical treatment may allow bacteria to enter the body (eg during surgery) or it may deplete their immune system, which reduces the body's ability to fight off infection (eg during cancer treatment or organ transplantation). Thus antibiotic resistance may have an adverse effect on our ability to deliver modern medicine safely.

The potential problem of antibiotic resistance is not new. It was first highlighted as long ago as 1945 when Sir Alexander Fleming, the discoverer of penicillin, stated in his Nobel acceptance speech that penicillin underdosage might give rise to penicillin resistance.

Here we are some 70 years later with not much progress in tackling the problem of antibiotic resistance. Bacteria have developed powerful survival pathways in order to protect themselves from external toxins. The frequency of antibiotic resistance in a bacterial culture is in the order of one antibiotic resistant mutation in 100 million bacteria. For every antibiotic already in clinical use resistant bacteria have arisen.

The situation is dire since commensal bacteria such as E.coli and S. aureus can become resistant to multiple antibiotics. It is likely that we all carry drug resistant bacteria in our bodies but these are controlled by our immune systems. When our immune systems are compromised for example after cancer chemotherapy, then the resistant bacteria can grow unchecked leading to severe infection and sometimes death.

The World Health Organisation said in a report published in 2012 that if no action was taken medicine as it is currently practiced would become more and more difficult. The US President's commission, the UK's chief medical officer Dame Sally Davies and the Prime Minister David Cameron have all highlighted the seriousness of the antibiotic resistance problem and stated something must be done urgently to avoid medicine going back to the dark ages. The PM has created the O'Neill commission to look into why no new antibiotics have been developed over the past 25 years and to seek new financial incentives to stimulate antibiotic research.

25,000 people die each year in Europe from antibiotic resistant infections and 5,000 people in the United Kingdom – the incidence is rising. Every year 35,000 people die from sepsis in the UK – some of these deaths are from antibiotic resistant infections. It has been estimated that if no new antibiotics are introduced within the next 7-10 years, we could face a public health crisis where today's routine medical procedures could become life threatening.

Most of the antibiotics we use today were developed some 20 or more years ago. Only two new antibiotic classes have been developed since the golden age of antibiotic development in the 1950s and 60s. Most of the large pharmaceutical companies have closed down their antibiotic research development programmes citing a lack of financial return and have focused on other areas such as cancer and heart disease where patients take drugs for many years as opposed to antibiotics where treatments are short.

Frustrated by the lack of action by government and the pharmaceutical industry as well as very limited research funding (less than 1% of the UK medical research budget), a network known as Antibiotic Discovery UK, consisting of leading UK scientists and clinicians drawn from a dozen of the country's top universities as well as small company representatives, determined that a new charity should be created to find new drugs to treat antibiotic resistant infections. Named Antibiotic Research UK (ANTRUK) the charity is the world's first dedicated to developing new antibiotics against antibiotic resistant infections. It has also been chosen by the UK's BioIndustry Association (BIA) as its charity of 2015.

Typically it can take up to 15 years and expenditure of many hundreds of millions of pounds to develop a new drug. ANTRUK aims to short circuit these timelines and costs by using smart approaches which will be different to normal drug development procedures.

In particular the charity will focus on repurposing or repositioning existing drugs. This could involve

  1. Taking drugs that are currently used for one indication such as cancer treatment or heart disease and examining them for antibiotic activity
  2. Combining two existing antibiotics to see if they can overcome antibiotic resistance or
  3. Combining one or more drugs together with the antibiotic to see if the antibiotic resistance can be overcome (antibiotic resistance breakers).

Its ultimate goal is to find at least one new therapy against antibiotic resistant bacteria by 2020 with further therapies being developed over the next decade.

Article by
Prof Colin Garner

is chief executive, Antibiotic Research UK. Email him.

23rd December 2014

Article by
Prof Colin Garner

is chief executive, Antibiotic Research UK. Email him.

23rd December 2014

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